The present invention relates to ganglioside related compounds.
In general, glycolipids of mammal cells are the substances which are formed by glycoside linkage of various combinations of various sugars such as glucose, galactose, N-acetylglucosamine, N-acetylgalactosamine, fucose and sialic acid, with a lipid structure called ceramide which in turn is formed through an amide linkage of fatty acid with long-chain aminoalcohol known as sphingosine. And, these glycolipids belong to a so-called sphingoglycolipid. Among these glycolipids, those which have sialic acid are specifically called gangliosides.
Generally, such compounds exist locally in the outer molecular layer of the bi-layer structure of the cell membrane. The current study has proved that these compounds play important roles in cells, such as identification of cells, reception and response to information, receptor function, differentiation, and proliferation, malignant alteration and behavior of cells, and so forth.
Among these gangliosides, Ganglioside GM.sub.1 was first discovered by Kuhn, Wiegandt and others in human brains and calf brains. It is known that Ganglioside GM.sub.1 has a structure expressed by the following general formula: ##STR3##
However, R.sub.1 and R.sub.2 of the ceramide portion have not yet been specified.
In fact, it is known that Ganglioside GM.sub.1 acts as a receptor. For instance, it is known that this substance is bonded to cholera toxin protein, and changes the conformation of the protein, thereby activating adenylate cyclase and raising the level of generation of cyclic AMP, which in turn causes dehydration. Recent studies have also made it clear that Ganglioside GM.sub.1 acts as an intermediary in proliferation of brain glandula lymphocytes (SCIENCE, Vol. 230, pp. 1285-1287, published on Dec. 13, 1985).
Ganglioside GM.sub.2 can also be isolated from brains, nervous tissues, brains of patients suffering from Tay Sach disease, lymphomas of mice, fibroblasts, livers of rats, and cancer tissues of livers. It is known that Ganglioside GM.sub.2 has a structure expressed by the following general formula: ##STR4##
However, the R.sub.1 and R.sub.2 of the ceramide group have not yet been specified.
It is considered that Ganglioside GM.sub.2 is able to function as a cancer-related antigen marker useful for diagnosis and therapy of cancers. It is also known that, since the action of interferon against virus infection is neutralized by Ganglioside GM.sub.2, the production of interferon can be induced by adding Ganglioside GM.sub.2 to mice cells which are inactive to interferon.
In spite of the fact that Gangliosides GM.sub.1 and GM.sub.2 are known to have various biochemical functions, it has been difficult to isolate Gangliosides GM.sub.1 and GM.sub.2 and their related compounds from a living body and refine them, and complete synthesis of Gangliosides GM.sub.1 and GM.sub.2 and their related compounds has not been accomplished, yet. Fine syntheses of Gangliosides GM.sub.1 and GM.sub.2 compounds related thereto in are absolutely necessary to clarify the correlation between the molecular structures of these Gangliosides and biological information.
On the other hand, a ganglioside called a cancer antigen which can be isolated, from colon and liver cancer tissues is peculiar to those tissues. It is thought that this substance is closely related to the immune system of a body suffering from such a disease. However, it has been difficult to obtain this compound through the operations of extraction, isolation and purification. The supply of this compound and analogous compounds as a pure substance enables them to be used for tracing antigen-antibody reactions and preparing monoclonal antibodies, and is thus thought to be very important from the viewpoint of pharmaceutics (Biochem. Biophys. Res. Commun., vol. 113, 791-798 (1983)).
Further, it has been found that Ganglioside GD.sub.1a is isolated from nervous tissues or the brain of a patient suffering from Tay Sach disease.
It is thought that Ganglioside GD.sub.1a can serve as a cancer related antigen marker for diagnosis and remedies of cancer.
Although it is found that Ganglioside GD.sub.1a has various biological functions, it is difficult to isolate Ganglioside GD.sub.1a and compounds related thereto from living bodies and to purify them, and the complete analyses thereof have not so far been achieved.
Therefore, the fine syntheses of those gangliosides and compounds related thereto in a sterically selective manner are absolutely necessary for clarification of the correlation between biological information and the molecular structures of these gangliosides compounds.